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I Am Intramural

Is the Yanny vs. Laurel debate tearing your office or lab apart? Well, according to NIH IRP investigators, there's no true answer to what this word is. As brain expert Mark Hallett, M.D., of the NIH National Institute of Neurological Disorders and Stroke puts it, "Perception is not reality, however real it seems."

It might seem easy to blame your parents for the way you turned out; after all, they raised you and gave you all of your DNA. But, before throwing blame around, consider saving some for the place where you grew up. According to new IRP research, being raised in an urban environment can dramatically alter how your genes influence your brain.1

NIH history is rife with legends, scientists who have made remarkable discoveries and incalculable contributions to the health and longevity of humankind. There are living legends; just peruse the “Honors” page on the IRP website to see what I mean. And there are greats who are gone but certainly not forgotten.

James F. Holland, M.D., a renowned cancer expert who was a major figure in the development of cancer chemotherapy, died on March 22, 2018, at the age of 92. Dr. Holland was among the first group of research physicians recruited to the NIH Clinical Center, serving as a senior surgeon at the National Cancer Institute from 1953 to 1954. In that short year at the NIH, he initiated a clinical trial to compare continuous or intermittent treatment with two chemotherapy agents for acute leukemia in children: methotrexate and 6-mercaptopurine. Dr. Holland moved to Roswell Park Memorial Institute in Buffalo before the trial was completed, but he continued to collaborate. His work ultimately turned an incurable illness into one with an 80% survival rate. In 1972, he and his NIH collaborators shared the Albert Lasker Clinical Medical Research Award for "outstanding contribution to the concept and application of combination therapy in the treatment of acute leukemia in children."

On Wednesday, May 2, hundreds of researchers gathered at NIH’s Natcher Conference Center to show off their recent discoveries. But unlike a typical scientific conference, the letters “M.D.” and “Ph.D.” were noticeably absent from these scientists’ credentials. Instead, the event — NIH’s annual Postbac Poster Day — celebrated the accomplishments of individuals participating in the NIH Postbaccalaureate Intramural Research Training Award (IRTA) Program.

Most people experience anxiety at some point in their lives, whether it’s pre-speech jitters or sweaty palms when their plane takes off. While mild feelings of nervousness are completely normal and can even be beneficial, anxiety can also have negative repercussions if it causes somebody to completely avoid situations like social encounters or taking a flight to visit distant family.

Ever since the Human Genome Project (HGP) launched in 1990, patients and members of the public have been inundated with predictions about how unraveling the mysteries of genetics will revolutionize healthcare. Today, many of these promises remain unrealized, prompting some to become skeptical of the true utility of this research for improving human health. But, while more work is needed to fully realize the potential of genome-focused medicine, it remains true that patients are benefiting from our knowledge of the human genome in numerous, sometimes under-appreciated ways.

In the midst of the 1957 Asian flu pandemic, doctors and researchers were understandably focused on treating patients and developing ways to contain the outbreak. It wasn’t until 30 years later that scientists began reporting that women who were pregnant when they caught the virus were more likely to have children who would later be diagnosed with schizophrenia.1 While that relationship remains controversial,2 numerous studies have since linked activation of a pregnant woman’s immune system with an increased risk that her child will develop certain psychiatric disorders, including not just schizophrenia but also autism spectrum disorder and major depressive disorder.3 A new IRP study has now expanded on this work by showing that exposure to higher levels of two immune system molecules in utero can noticeably alter the neurological and cognitive development of young children.4

Every forty seconds, someone in the United States suffers a stroke, and researchers across the country are hunting for a way to help brain cells survive these traumatic events. A group of IRP researchers recently discovered a promising new tool to aid in this effort. By blocking the action of a brain chemical called monoacylglycerol lipase (MAGL), the scientists markedly reduced stroke-related brain damage and disability in rats.1

Alex Fuksenko, a senior at the University of Maryland in College Park, spent his summer in the lab of NIH IRP Investigator Kevin Briggman, Ph.D.

Fuksenko helped to create a website called Labrainth that “gamifies” the identification and tracing of neurons in 2D images produced by electron microscopes. By visiting the website and completing those activities, members of the public can earn points and move up leaderboards while producing data that machine learning algorithms can use to learn how to trace neurons in these images themselves, a necessary step towards producing an accurate 3D model of the human brain.

Like a bear leaves its ominous footprints in the snow, diseases and other biological processes often leave traces throughout our bodies. Recent technological and scientific advances have enabled clinicians to use measurements of these ‘biomarkers’ in their attempts to improve our health. A new studyby IRP researchers revealed that patients with a sleep disorder called obstructive sleep apnea (OSA) have higher blood concentrations of certain biomarkers that may foreshadow poor brain health later in life.1

When people with OSA sleep, their throat muscles relax and block their windpipes, preventing proper breathing and often waking them up. As a result, these individuals get lower-quality sleep and their brains receive less oxygen at night.

“The overall idea is that those two conditions are not good for brain health, but nobody had really looked to see if some of the biomarkers we see in brain injury are also common in younger individuals with this type of disordered breathing,” says IRP Lasker Clinical Research Scholar Jessica Gill, Ph.D., R.N., the study’s senior author.

Food companies have long marketed carbohydrate-rich drinks and energy bars to athletes with the message that the energy those snacks provide is key to lifting heavier and running farther. A new mouse study by IRP researchers, however, suggests that skipping a meal (or several) might be far more effective for increasing athletic prowess1.

Unlike modern Americans used to three square meals a day, our ancient ancestors couldn’t exactly throw a TV dinner in the microwave whenever they felt a bit peckish. As a result, they probably found themselves hunting wooly mammoths and fending off saber-toothed tigers on an empty stomach.

“From an evolutionary perspective, animals in the wild – particularly predators – need to be able to function at a high level when they’re in a food-deprived state,” says IRP Senior Investigator Mark P. Mattson, Ph.D., the study’s senior author. “Individuals who were able to perform at a high level in a fasted state had a survival advantage.”

After postdoctoral fellows in biomedical research complete their training, they are prepared to land permanent positions that utilize their unique research skills. While some may choose the traditional academic route, and become tenure-track scientists, many take posts that keep them engaged in science, but not necessarily doing research.

Once confined to the realms of science fiction, virtual reality (VR) has crossed over into the real world in a wide array of fields, including scientific research and clinical medicine. In the IRP, several researchers are utilizing the cutting-edge technology in their efforts to improve human health.

Susan Persky, Ph.D., for instance, runs the Immersive Virtual Environment Test Unit, where she uses VR to simulate how genetic information might affect doctor-patient interactions and influence patients’ emotions, beliefs, and decisions. She has also put the technology to use studying the food choices of overweight and obese individuals by presenting them with a simulated buffet. Meanwhile, John Ostuni, Ph.D., explores how VR might help doctors diagnose or treat patients, such as by providing access to physical therapy without going to the hospital. And Victor Cid, M.S., creates virtual reality scenarios for the Disaster Information Management Research Center that can train emergency personnel how to more effectively respond to major crises.

On Friday, February 23, they joined several NIH colleagues for a Reddit “Ask Me Anything” (AMA) to answer questions from the public about how virtual reality might change the way medicine and research are practiced and ultimately make people’s lives better. Read on for some of the most interesting exchanges that took place or check out the full AMA on Reddit.

Carly Kaplan, a junior at Brown University in Providence, Rhode Island, spent her summer working in the lab of NIH IRP Investigator Dr. Kareem Zaghloul. As a member of Dr. Zaghloul’s team, Carly examined how the human brain creates and recalls memories. An aspiring doctor, she believes that this sort of research is “the backbone of the medical profession” and that “doctors can’t do what they do without the research behind it.” While at NIH, she was particularly intrigued by the opportunity to watch Dr. Zaghloul perform neurosurgery on the epilepsy patients who were part of in his lab’s studies.

Between 25 and 30 million Americans have a rare disease, defined as a condition affecting fewer than 200,000 people. On March 1, the NIH will host its annual Rare Disease Day to increase awareness of these under-recognized and often undiagnosed illnesses and highlight the efforts of scientists, patients, and advocates to produce treatments.

In anticipation of the occasion, on February 23, NIH organized a Twitter chat with NIH Director Francis Collins, M.D., Ph.D., and Sharon Terry, President and CEO of Genetic Alliance and a member of the Research Program Advisory Panel for NIH’s All of US project. Check out some of the more noteworthy exchanges below or look at the full Twitter chat by searching for #NIHchat on Twitter.

In one of Aesop’s classic fables, a clever wolf dons a sheep’s skin in order to move through the herd undetected. As it turns out, IRP researchers have discovered that in people with a specific set of immune system genes, the HIV virus uses a similar approach to hide from the body’s defenses.1

Nearly all cells in our bodies are coated with proteins called human leukocyte antigens (HLAs). These proteins allow the immune system to distinguish between healthy, native cells and those contaminated by unwelcome visitors like viruses or bacteria that must be destroyed. Each of the various HLA proteins is encoded by a different HLA gene and these genes vary considerably between individuals, causing different people to have different variants of each HLA protein.

“There are thousands of different forms of these HLA genes, and that variation allows us, as a species, to deal with virtually all infectious pathogens,” says IRP Senior Investigator Mary N. Carrington, Ph.D., the senior author of the new paper. “We’re really interested in the diversity of that part of the genome, since the risk of essentially every autoimmune disease, many cancers, and probably every infectious disease is associated with this set of genes.”

For over a decade, my family shared our home with a short, fat beagle named Kayla Sue. She had big floppy ears, a tail as straight as an exclamation point, and a coat of fur that was a patchwork of white, brown, and black splotches. Her love of chasing small animals was matched only by her enthusiasm for eating, napping, and belly rubs. One of my best friends growing up, on the other hand, had a mean-spirited Dachshund named Rocky who would not let anyone outside his family touch his long, brown, sausage-shaped body. Meanwhile, one of my brother’s close childhood friends had two humongous, overly-friendly, black-and-brown German shepherds that would immediately bowl you over when you walked through the front door.

It doesn’t take a particularly sharp observer to notice that, despite being the same species, the more than 300 breeds of dog have remarkably different physical and behavioral traits. But what remains less clear even today are the specific biological roots that produce these widely varying attributes. And, perhaps more importantly, scientists seek to understand how learning about that immense diversity might help us improve the health of our canine companions – and ourselves.

On December 22, 2015, the United Nations General Assembly adopted a resolution proclaiming February 11 of each year as the International Day of Women and Girls in Science, with the goal of highlighting the important contributions of women to the fields of science, technology, engineering, and mathematics. Here at NIH, a dedicated group of scientists known as the Women Scientist Advisors (WSA) is working not only to recognize the role of women in the biomedical sciences but to expand it as well.

Researchers have a long history of fattening up mice to gain insight into the causes and consequences of weight gain in the human body. In one of the more recent studies of this kind, a team of IRP researchers found that that a high-fat diet consistently altered the collection of microbes residing in mice’s digestive tracts and that this diet-microbe combination might pre-dispose the mice – and, potentially, obese humans – to colon cancer by triggering certain changes in how genes behave.